TY  - JOUR
A1  - Scheer, Nico
A1  - Wilson, Ian D.
T1  - A comparison between genetically humanized and chimeric liver humanized mouse models for studies in drug metabolism and toxicity
JF  - Drug Discovery Today
N2  - Mice that have been genetically humanized for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging and promising in vivo models for an improved prediction of the pharmacokinetic, drug–drug interaction and safety characteristics of compounds in humans. The specific advantages and disadvantages of these models should be carefully considered when using them for studies in drug discovery and development. Here, an overview on the corresponding genetically humanized and chimeric liver humanized mouse models described to date is provided and illustrated with examples of their utility in drug metabolism and toxicity studies. We compare the strength and weaknesses of the two different approaches, give guidance for the selection of the appropriate model for various applications and discuss future trends and perspectives.
Y1  - 2016
U6  - http://dx.doi.org/10.1016/j.drudis.2015.09.002
SN  - 1359-6446
VL  - 21
IS  - 2
SP  - 250
EP  - 263
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Svaneborg, Carsten
A1  - Karimi-Varzaneh, Hossein Ali
A1  - Hojdis, Nils
A1  - Fleck, Franz
A1  - Everaers, Ralf
T1  - Multiscale approach to equilibrating model polymer melts
JF  - Physical Review E
N2  - We present an effective and simple multiscale method for equilibrating Kremer Grest model polymer melts of varying stiffness. In our approach, we progressively equilibrate the melt structure above the tube scale, inside the tube and finally at the monomeric scale. We make use of models designed to be computationally effective at each scale. Density fluctuations in the melt structure above the tube scale are minimized through a Monte Carlo simulated annealing of a lattice polymer model. Subsequently the melt structure below the tube scale is equilibrated via the Rouse dynamics of a force-capped Kremer-Grest model that allows chains to partially interpenetrate. Finally the Kremer-Grest force field is introduced to freeze the topological state and enforce correct monomer packing. We generate 15 melts of 500 chains of 10.000 beads for varying chain stiffness as well as a number of melts with 1.000 chains of 15.000 monomers. To validate the equilibration process we study the time evolution of bulk, collective, and single-chain observables at the monomeric, mesoscopic, and macroscopic length scales. Extension of the present method to longer, branched, or polydisperse chains, and/or larger system sizes is straightforward.
Y1  - 2016
U6  - http://dx.doi.org/10.1103/PhysRevE.94.032502
SN  - 2470-0053
VL  - 94
IS  - 032502
PB  - AIP Publishing
CY  - Melville, NY
ER  - 
TY  - JOUR
A1  - Schwab, Lukas
A1  - Hojdis, Nils
A1  - Lacayo, Jorge
A1  - Wilhelm, Manfred
T1  - Fourier-Transform Rheology of Unvulcanized, Carbon Black Filled Styrene Butadiene Rubber
JF  - Macromolecular Materials and Engineering
N2  - Rubber materials filled with reinforcing fillers display nonlinear rheological behavior at small strain amplitudes below γ0 < 0.1. Nevertheless, rheological data are analyzed mostly in terms of linear parameters, such as shear moduli (G′, G″), which loose their physical meaning in the nonlinear regime. In this work styrene butadiene rubber filled with carbon black (CB) under large amplitude oscillatory shear (LAOS) is analyzed in terms of the nonlinear parameter I3/1. Three different CB grades are used and the filler load is varied between 0 and 70 phr. It is found that I3/1(φ) is most sensitive to changes of the total accessible filler surface area at low strain amplitudes (γ0 = 0.32). The addition of up to 70 phr CB leads to an increase of I3/1(φ) by a factor of more than ten. The influence of the measurement temperature on I3/1 is pronounced for CB levels above the percolation threshold.
Y1  - 2016
U6  - http://dx.doi.org/10.1002/mame.201500356
SN  - 1439-2054
VL  - 301
IS  - 4
SP  - 457
EP  - 468
PB  - Wiley-VCH
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - Harish, Ajay B.
A1  - Wriggers, Peter
A1  - Jungk, Juliane
A1  - Hojdis, Nils
A1  - Recker, Carla
T1  - Mesoscale Constitutive Modeling of Non-Crystallizing Filled Elastomers
JF  - Computational Mechanics
N2  - Elastomers are exceptional materials owing to their ability to undergo large deformations before failure. However, due to their very low stiffness, they are not always suitable for industrial applications. Addition of filler particles provides reinforcing effects and thus enhances the material properties that render them more versatile for applications like tyres etc. However, deformation behavior of filled polymers is accompanied by several nonlinear effects like Mullins and Payne effect. To this day, the physical and chemical changes resulting in such nonlinear effect remain an active area of research. In this work, we develop a heterogeneous (or multiphase) constitutive model at the mesoscale explicitly considering filler particle aggregates, elastomeric matrix and their mechanical interaction through an approximate interface layer. The developed constitutive model is used to demonstrate cluster breakage, also, as one of the possible sources for Mullins effect observed in non-crystallizing filled elastomers.
Y1  - 2016
U6  - http://dx.doi.org/10.1007/s00466-015-1251-1
SN  - 1432-0924
VL  - 57
SP  - 653
EP  - 677
PB  - Springer
CY  - Berlin
ER  - 
TY  - JOUR
A1  - Muschallik, Lukas
A1  - Molinnus, Denise
A1  - Bongaerts, Johannes
A1  - Pohl, Martina
A1  - Wagner, Torsten
A1  - Schöning, Michael Josef
A1  - Siegert, Petra
A1  - Selmer, Thorsten
T1  - (R,R)-Butane-2,3-diol Dehydrogenase from Bacillus clausii DSM 8716T: Cloning and Expression of the bdhA-Gene, and Initial Characterization of Enzyme
JF  - Journal of Biotechnology
N2  - The gene encoding a putative (R,R)-butane-2,3-diol dehydrogenase (bdhA) from Bacillus clausii DSM 8716T was isolated, sequenced and expressed in Escherichia coli. The amino acid sequence of the encoded protein is only distantly related to previously studied enzymes (identity 33–43%) and exhibited some uncharted peculiarities. An N-terminally StrepII-tagged enzyme variant was purified and initially characterized. The isolated enzyme catalyzed the (R)-specific oxidation of (R,R)- and meso-butane-2,3-diol to (R)- and (S)-acetoin with specific activities of 12 U/mg and 23 U/mg, respectively. Likewise, racemic acetoin was reduced with a specific activity of up to 115 U/mg yielding a mixture of (R,R)- and meso-butane-2,3-diol, while the enzyme reduced butane-2,3-dione (Vmax 74 U/mg) solely to (R,R)-butane-2,3-diol via (R)-acetoin. For these reactions only activity with the co-substrates NADH/NAD+ was observed. The enzyme accepted a selection of vicinal diketones, α-hydroxy ketones and vicinal diols as alternative substrates. Although the physiological function of the enzyme in B. clausii remains elusive, the data presented herein clearly demonstrates that the encoded enzyme is a genuine (R,R)-butane-2,3-diol dehydrogenase with potential for applications in biocatalysis and sensor development.
Y1  - 2017
U6  - http://dx.doi.org/10.1016/j.jbiotec.2017.07.020
SN  - 0168-1656
VL  - 258
SP  - 41
EP  - 50
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Röhlen, Desiree
A1  - Pilas, Johanna
A1  - Schöning, Michael Josef
A1  - Selmer, Thorsten
T1  - Development of an amperometric biosensor platform for the combined determination of l-Malic, Fumaric, and l-Aspartic acid
JF  - Applied Biochemistry and Biotechnology
N2  - Three amperometric biosensors have been developed for the detection of L-malic acid, fumaric acid, and L -aspartic acid, all based on the combination of a malate-specific dehydrogenase (MDH, EC 1.1.1.37) and diaphorase (DIA, EC 1.8.1.4). The stepwise expansion of the malate platform with the enzymes fumarate hydratase (FH, EC 4.2.1.2) and aspartate ammonia-lyase (ASPA, EC 4.3.1.1) resulted in multi-enzyme reaction cascades and, thus, augmentation of the substrate spectrum of the sensors. Electrochemical measurements were carried out in presence of the cofactor β-nicotinamide adenine dinucleotide (NAD+) and the redox mediator hexacyanoferrate (III) (HCFIII). The amperometric detection is mediated by oxidation of hexacyanoferrate (II) (HCFII) at an applied potential of + 0.3 V vs. Ag/AgCl. For each biosensor, optimum working conditions were defined by adjustment of cofactor concentrations, buffer pH, and immobilization procedure. Under these improved conditions, amperometric responses were linear up to 3.0 mM for L-malate and fumarate, respectively, with a corresponding sensitivity of 0.7 μA mM−1 (L-malate biosensor) and 0.4 μA mM−1 (fumarate biosensor). The L-aspartate detection system displayed a linear range of 1.0–10.0 mM with a sensitivity of 0.09 μA mM−1. The sensor characteristics suggest that the developed platform provides a promising method for the detection and differentiation of the three substrates.
Y1  - 2017
U6  - http://dx.doi.org/10.1007/s12010-017-2578-1
SN  - 1559-0291
VL  - 183
SP  - 566
EP  - 581
PB  - Springer
CY  - Berlin
ER  - 
TY  - JOUR
A1  - Pilas, Johanna
A1  - Yazici, Yasemen
A1  - Selmer, Thorsten
A1  - Keusgen, Michael
A1  - Schöning, Michael Josef
T1  - Optimization of an amperometric biosensor array for simultaneous measurement of ethanol, formate, d- and l-lactate
JF  - Electrochimica Acta
N2  - The immobilization of NAD+-dependent dehydrogenases, in combination with a diaphorase, enables the facile development of multiparametric sensing devices. In this work, an amperometric biosensor array for simultaneous determination of ethanol, formate, d- and l-lactate is presented. Enzyme immobilization on platinum thin-film electrodes was realized by chemical cross-linking with glutaraldehyde. The optimization of the sensor performance was investigated with regard to enzyme loading, glutaraldehyde concentration, pH, cofactor concentration and temperature. Under optimal working conditions (potassium phosphate buffer with pH 7.5, 2.5 mmol L-1 NAD+, 2.0 mmol L-1 ferricyanide, 25 °C and 0.4% glutaraldehyde) the linear working range and sensitivity of the four sensor elements was improved. Simultaneous and cross-talk free measurements of four different metabolic parameters were performed successfully. The reliable analytical performance of the biosensor array was demonstrated by application in a clarified sample of inoculum sludge. Thereby, a promising approach for on-site monitoring of fermentation processes is provided.
KW  - Simultaneous determination
KW  - Enzymatic biosensor
KW  - Diaphorase
KW  - Dehydrogenase
Y1  - 2017
U6  - http://dx.doi.org/10.1016/j.electacta.2017.07.119
SN  - 0013-4686
VL  - 251
SP  - 256
EP  - 262
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Seifarth, Volker
A1  - Grosse, Joachim O.
A1  - Grossmann, Matthias
A1  - Janke, Heinz Peter
A1  - Arndt, Patrick
A1  - Koch, Sabine
A1  - Epple, Matthias
A1  - Artmann, Gerhard
A1  - Temiz Artmann, Aysegül
T1  - Mechanical induction of bi-directional orientation of primary porcine bladder smooth muscle cells in tubular fibrin-poly(vinylidene fluoride) scaffolds for ureteral and urethral repair using cyclic and focal balloon catheter stimulation
JF  - Journal of Biomaterials Applications
Y1  - 2017
U6  - http://dx.doi.org/10.1177/0885328217723178
SN  - 1530-8022
VL  - 32
IS  - 3
SP  - 321
EP  - 330
PB  - Sage
CY  - London
ER  - 
TY  - JOUR
A1  - Breuer, Lars
A1  - Mang, Thomas
A1  - Schöning, Michael Josef
A1  - Thoelen, Ronald
A1  - Wagner, Torsten
T1  - Investigation of the spatial resolution of a laser-based stimulation process for light-addressable hydrogels with incorporated graphene oxide by means of IR thermography
JF  - Sensors and Actuators A: Physical
Y1  - 2017
U6  - http://dx.doi.org/10.1016/j.sna.2017.11.031
SN  - 0924-4247
VL  - 268
SP  - 126
EP  - 132
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Demmer, Julius K.
A1  - Chowdhury, Nilanjan Pal
A1  - Selmer, Thorsten
A1  - Ermler, Ulrich
A1  - Buckel, Wolfgang
T1  - The semiquinone swing in the bifurcating electron transferring flavoprotein/butyryl-CoA dehydrogenase complex from Clostridium difficile
JF  - Nature Communications
Y1  - 2017
U6  - http://dx.doi.org/10.1038/s41467-017-01746-3
SN  - 2041-1723
N1  - Article number 1577
VL  - 8
IS  - 1
SP  - 1
EP  - 10
ER  - 
TY  - JOUR
A1  - Werkhausen, Amelie
A1  - Albracht, Kirsten
A1  - Cronin, Neil J.
A1  - Meier, Rahel
A1  - Mojsen-Moeller, Jens
A1  - Seynnes, Olivier R.
T1  - Modulation of muscle-tendon interaction in the human triceps surae during an energy dissipation task
JF  - Journal of Experimental Biology
Y1  - 2017
U6  - http://dx.doi.org/10.1242/jeb.164111
SN  - 0022-0949
VL  - 220
IS  - 22
SP  - 4141
EP  - 4149
ER  - 
TY  - JOUR
A1  - Liu, Z.
A1  - Schaap, K. S.
A1  - Ballemans, L.
A1  - de Blois, E.
A1  - Rohde, M.
A1  - Paulßen, Elisabeth
T1  - Measurement of reaction kinetics of [177Lu]Lu-DOTA-TATE using a microfluidic system
JF  - Dalton Transactions
Y1  - 2017
U6  - http://dx.doi.org/10.1039/C7DT01830D
SN  - 1477-9234
VL  - 46
IS  - 42
SP  - 14669
EP  - 14676
ER  - 
TY  - JOUR
A1  - Wilson, Ian D.
A1  - Wilson, Claire E.
A1  - Scheer, Nico
A1  - Dickie, A.P.
A1  - Schreiter, K.
A1  - Wilson, E. M.
A1  - Riley, R. J.
A1  - Wehr, R.
A1  - Bial, J.
T1  - The Pharmacokinetics and Metabolism of Lumiracoxib in Chimeric Humanized and Murinized FRG Mice
JF  - Biochemical pharmacology
Y1  - 2017
U6  - http://dx.doi.org/10.1016/j.bcp.2017.03.015
SN  - 1873-2968
VL  - Volume 135
SP  - 139
EP  - 150
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Mayer, Jan
A1  - Hentschke, Reinhard
A1  - Hager, Jonathan
A1  - Hojdis, Nils
A1  - Karimi-Varnaneh, Hossein Ali
T1  - A Nano-Mechanical Instability as Primary Contribution to Rolling Resistance
JF  - Scientific Reports
Y1  - 2017
SN  - 2045-2322
VL  - 7
IS  - Article number 11275
PB  - Springer
CY  - Berlin
ER  - 
TY  - JOUR
A1  - Meyer, Jan
A1  - Hentschke, Reinhard
A1  - Hager, Jonathan
A1  - Hojdis, Nils
A1  - Karimi-Varzaneh, Hossein Ali
T1  - Molecular Simulation of Viscous Dissipation due to Cyclic Deformation of a Silica–Silica Contact in Filled Rubber
JF  - Macromolecules
Y1  - 2017
U6  - http://dx.doi.org/10.1021/acs.macromol.7b00947
SN  - 1520-5835
VL  - 50
IS  - 17
SP  - 6679
EP  - 6689
ER  - 
TY  - JOUR
A1  - Druckenmüller, Katharina
A1  - Günther, Klaus
A1  - Elbers, Gereon
T1  - Near-infrared spectroscopy (NIRS) as a tool to monitor exhaust air from poultry operations
JF  - Science of the Total Environment
N2  - Intensive poultry operation systems emit a considerable volume of inorganic and organic matter in the surrounding environment. Monitoring cleaning properties of exhaust air cleaning systems and to detect small but significant changes in emission characteristics during a fattening cycle is important for both emission and fattening process control. In the present study, we evaluated the potential of near-infrared spectroscopy (NIRS) combined with chemometric techniques as a monitoring tool of exhaust air from poultry operation systems. To generate a high-quality data set for evaluation, the exhaust air of two poultry houses was sampled by applying state-of-the-art filter sampling protocols. The two stables were identical except for one crucial difference, the presence or absence of an exhaust air cleaning system. In total, twenty-one exhaust air samples were collected at the two sites to monitor spectral differences caused by the cleaning device, and to follow changes in exhaust air characteristics during a fattening period. The total dust load was analyzed by gravimetric determination and included as a response variable in multivariate data analysis. The filter samples were directly measured with NIR spectroscopy. Principal component analysis (PCA), linear discriminant analysis (LDA), and factor analysis (FA) were effective in classifying the NIR exhaust air spectra according to fattening day and origin. The results indicate that the dust load and the composition of exhaust air (inorganic or organic matter) substantially influence the NIR spectral patterns. In conclusion, NIR spectroscopy as a tool is a promising and very rapid way to detect differences between exhaust air samples based on still not clearly defined circumstances triggered during a fattening period and the availability of an exhaust air cleaning system.
Y1  - 2018
U6  - http://dx.doi.org/10.1016/j.scitotenv.2018.02.072
SN  - 0048-9697
VL  - 630
SP  - 536
EP  - 543
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Molinnus, Denise
A1  - Muschallik, Lukas
A1  - Gonzalez, Laura Osorio
A1  - Bongaerts, Johannes
A1  - Wagner, Torsten
A1  - Selmer, Thorsten
A1  - Siegert, Petra
A1  - Keusgen, Michael
A1  - Schöning, Michael Josef
T1  - Development and characterization of a field-effect biosensor for the detection of acetoin
JF  - Biosensors and Bioelectronics
N2  - A capacitive electrolyte-insulator-semiconductor (EIS) field-effect biosensor for acetoin detection has been presented for the first time. The EIS sensor consists of a layer structure of Al/p-Si/SiO₂/Ta₂O₅/enzyme acetoin reductase. The enzyme, also referred to as butane-2,3-diol dehydrogenase from B. clausii DSM 8716T, has been recently characterized. The enzyme catalyzes the (R)-specific reduction of racemic acetoin to (R,R)- and meso-butane-2,3-diol, respectively. Two different enzyme immobilization strategies (cross-linking by using glutaraldehyde and adsorption) have been studied. Typical biosensor parameters such as optimal pH working range, sensitivity, hysteresis, linear concentration range and long-term stability have been examined by means of constant-capacitance (ConCap) mode measurements. Furthermore, preliminary experiments have been successfully carried out for the detection of acetoin in diluted white wine samples.
Y1  - 2018
U6  - http://dx.doi.org/10.1016/j.bios.2018.05.023
VL  - 115
SP  - 1
EP  - 6
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Pilas, Johanna
A1  - Yazici, Y.
A1  - Selmer, Thorsten
A1  - Keusgen, M.
A1  - Schöning, Michael Josef
T1  - Application of a portable multi-analyte biosensor for organic acid determination in silage
JF  - Sensors
N2  - Multi-analyte biosensors may offer the opportunity to perform cost-effective and rapid analysis with reduced sample volume, as compared to electrochemical biosensing of each analyte individually. This work describes the development of an enzyme-based biosensor system for multi-parametric determination of four different organic acids. The biosensor array comprises five working electrodes for simultaneous sensing of ethanol, formate, d-lactate, and l-lactate, and an integrated counter electrode. Storage stability of the biosensor was evaluated under different conditions (stored at +4 °C in buffer solution and dry at −21 °C, +4 °C, and room temperature) over a period of 140 days. After repeated and regular application, the individual sensing electrodes exhibited the best stability when stored at −21 °C. Furthermore, measurements in silage samples (maize and sugarcane silage) were conducted with the portable biosensor system. Comparison with a conventional photometric technique demonstrated successful employment for rapid monitoring of complex media.
Y1  - 2018
U6  - http://dx.doi.org/10.3390/s18051470
SN  - 1424-8220
VL  - 18
IS  - 5
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Aboulnaga, E. A.
A1  - Zou, H.
A1  - Selmer, Thorsten
A1  - Xian, M.
T1  - Development of a plasmid-based, tunable, tolC-derived expression system for application in Cupriavidus necator H16
JF  - Journal of Biotechnology
N2  - Cupriavidus necator H16 gains increasing attention in microbial research and biotechnological application due to its diverse metabolic features. Here we present a tightly controlled gene expression system for C. necator including the pBBR1-vector that contains hybrid promoters originating from C. necator native tolC-promoter in combination with a synthetic tetO-operator. The expression of the reporter gene from these plasmids relies on the addition of the exogenous inducer doxycycline (dc). The novel expression system offers a combination of advantageous features as; (i) high and dose-dependent recombinant protein production, (ii) tight control with a high dynamic range (On/Off ratio), which makes it applicable for harmful pathways or for toxic protein production, (iii) comparable cheap inducer (doxycycline, dc), (iv) effective at low inducer concentration, that makes it useful for large scale application, (v) rapid, diffusion controlled induction, and (vi) the inducer does not interfere within the cell metabolism. As applications of the expression system in C. necator H16, the growth ability on glycerol was enhanced by constitutively expressing the E. coli glpk gene-encoding for glycerol kinase. Likewise, we used the system to overcome the expression toxicity of mevalonate pathway in C. necator H16. With this system, the mevalonate-genes were successfully introduced in the host and the recombinant strains could produce about 200 mg/l mevalonate.
Y1  - 2018
U6  - http://dx.doi.org/10.1016/j.jbiotec.2018.03.007
SN  - 0168-1656
VL  - 274
SP  - 15
EP  - 27
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Teumer, T.
A1  - Capitain, C.
A1  - Ross-Jones, J.
A1  - Tippkötter, Nils
A1  - Rädle, M.
A1  - Methner, F.-J.
T1  - In-line Haze Monitoring Using a Spectrally Resolved Back Scattering Sensor
JF  - BrewingScience
N2  - In the present work an optical sensor in combination with a spectrally resolved detection device for in-line particle-size-monitoring for quality control in beer production is presented. The principle relies on the size and wavelength dependent backscatter of growing particles in fluids. Measured interference structures of backscattered light are compared with calculated theoretical values, based on Mie-Theory, and fitted with a linear least square method to obtain particle size distributions. For this purpose, a broadband light source in combination with a process-CCD-spectrometer (charge ? coupled device spectrometer) and process adapted fiber optics are used. The goal is the development of an easy and flexible measurement device for in-line-monitoring of particle size. The presented device can be directly installed in product fill tubes or vessels, follows CIP- (cleaning in place) and removes the need of sample taking. A proof of concept and preliminary results, measuring protein precipitation, are presented.
Y1  - 2018
SN  - 1613-2041
VL  - 71
IS  - 5/6
SP  - 49
EP  - 55
PB  - Fachverlag Hans Carl
CY  - Nürnberg
ER  -